Point of No Return-What Is the Threshold of Mitochondria With Permeability Transition in Cells to Trigger Cell Death.

Programmed cell death (apoptosis) is essential part of the process of tissue regeneration that also plays role in the mechanism of pathology. The phenomenon of fast and transient permeability of mitochondrial membranes by various triggers, known as permeability transition pore (mPTP) leads to the release of proapoptotic proteins and acts as an initial step in initiation of apoptosis. However, a role for mPTP was also suggested for physiology and it is unclear if there is a threshold in number of mitochondria with mPTP which induces cell death and how this mechanism is regulated in different tissues.

The Role of Ion Channels and Intracellular Signaling Cascades in the Inhibitory Action of WIN 55,212-2 upon Hyperexcitation.

Gi-coupled receptors, particularly cannabinoid receptors (CBRs), are considered perspective targets for treating brain pathologies, including epilepsy. However, the precise mechanism of the anticonvulsant effect of the CBR agonists remains unknown. We have found that WIN 55,212-2 (a CBR agonist) suppresses the synchronous oscillations of the intracellular concentration of Ca ions (epileptiform activity) induced in the neurons of rat hippocampal neuron-glial cultures by bicuculline or NHCl.

Cell-Permeable HSP70 Protects Neurons and Astrocytes Against Cell Death in the Rotenone-Induced and Familial Models of Parkinson's Disease.

Heat shock protein 70 (HSP70) is activated under stress response. Its involvement in cell protection, including energy metabolism and quality control makes it a promising pharmacological target. A strategy to increase HSP70 levels inside the cells is the application of recombinant HSP70.

Impaired Mitochondrial Network Morphology and Reactive Oxygen Species Production in Fibroblasts from Parkinson's Disease Patients.

The mitochondrial network (MN) is a dynamic structure undergoing constant remodeling in the cell. It is assumed that perturbations to the MN may be associated with various pathologies, including Parkinson's disease (PD). Using automatic image analysis and super-resolution microscopy, we have assessed the MN parameters in fibroblasts from patients with established hereditary PD mutations (associated with PINK1, LRRK2, and α-synuclein, as well as PINK1 and Parkin proteins simultaneously) under normal conditions and after hydrogen peroxide-induced stress.

«One Small Step for Mouse»: High CO Inhalation as a New Therapeutic Strategy for Parkinson's Disease.

Parkinson's disease (PD) is a ubiquitous neurodegenerative disorder for which no effective treatment strategies are available. Existing pharmacotherapy is aimed only at correcting symptoms and slowing the progression of the disease, mainly by replenishing dopamine deficiency. It is assumed that mitochondrial dysfunction plays a key role in the pathogenesis of PD.